Spongeworthy genes

What are the key ingredients for making a multicellular animal, or metazoan? A couple of the fundamental elements are:

• A mechanism to allow informative interactions between cells. You don't want all the cells to be the same, you want them to communicate with one another and set up different fates. This is a process called cell signaling and the underlying process of turning a signal into a different pattern of gene or metabolic activity is called signal transduction.

• Patterns of differing cell adhesion. But of course! The cells of your multicellular animal better stick together, or the whole creature will fall apart. This can also be an important component of morphogenesis: switching on a particular adhesion molecule (by way of cell signaling, naturally) can cause one subset of cells to stick to one another more strongly than to their neighbors, and mechanical forces will then sort them out into different tissues.

These are extremely basic functions, sort of a minimal set of cellular activities that we need to have in place in order to even begin to consider evolving a metazoan. Fortunately for our evolutionary history, these are also useful functions for a single celled organism, and while the metazoa may have elaborated upon them to a high degree, there's nothing novel about the general processes in our make-up. The principles of signaling and transduction were first worked out in bacteria, and anyone who has a passing acquaintance with immunology will know about the adhesive properties of bacteria, and their propensity for modulating that adhesion to build complexes called biofilms.

So let's take a look at the distribution of signaling and adhesion molecules in single-celled organisms, multicellular animals, and most interestingly, a group that is close to the division between the two (although more on the side of multicellularity), the sponges.

Phylogenetic position of O. carmela (asterisk) relative to model bilaterians. Dd, D. discoideum; Sc, Saccharomyces cerevisiae; Sp, Schizosaccharomyces pombe; Oc, O. carmela; Dm, Drosophila melanogaster; Ce, Caenorhabditis elegans; Gg, Gallus gallus; Mm, Mus musculus;
Hs, Homo sapiens.

This cladogram illustrates the relationships of the organisms studied, and also, unfortunately, requires you to note a few non-standard acronyms.

First, a few non-metazoans on the left. "Dd" is the slime mold, Dictyostelium, which has amoeboid cells, and "Sc" and "Sp" are both yeasts, single-celled eukaryotes.

On the right are the true multicellular animals, or eumetazoa: "Dm" is the fly, Drosophila, "Ce" is the worm C. elegans, "Gg" is the chicken, Gallus, "Mm" is the mouse, Mus, and finally, of course, "Hs" is us, Homo sapiens. All of these organisms were selected because of the availability of comprehensive genomic data, and because they span a range of single-celled to multicellular organisms.

In the middle of the cladogram with an asterisk above its name is Oscarella carmela, the subject of this study. It's a sponge. Sponges are interesting because they're just barely multicellular: they only have a few cell types, no organs, only one kind of tissue, and their organization is extremely simple (still, it seems unfair to kick them out of the Eumetazoa, and as we'll see, their superficial simplicity hides an underlying complexity).

There's the question: what is the status of these essential components of the recipe for the metazoa in these organisms, the sponges, that are just above the threshold for multicellularity? To answer that question, I'm going to show you some humungous tables of data that might be a little bit intimidating, but don't panic— the message is going to be clear.

Here's how it works: the authors started with one species, the sponge O. carmela, that is not well characterized. They also had a list of known important molecules and their sequences, so they went fishing in a library of expressed gene sequences from the sponge to find which of these genes are present…and, basically, almost all of them are. The table lists on the left hand side the names of these genes, and then in addition, the authors searched genomic databases for 9 other well characterized species to see if they also had these genes. If they did, the entry is marked with a bullet (•); if not, an open symbol (◊). I think you'll see a pattern emerge fairly easily.

This first table lists the O. carmela signaling pathway genes. They fall into 6 classes: the Wnt pathway, TGFβ, Hedgehog, RTK, Jak/Stat, and Notch/Delta (there is a seventh common metazoan signaling family, the nuclear hormone receptor, which hasn't been found in the sponge.) They've also tossed two "Sp"s into the table: the bilaterian one is Strongylocentrotus purpuratus, the sea urchin.

Animal signaling-pathway components in the sponge O. carmela

Dixdc, Dix domain containing; Dkk, Dickkopf; Dvl, Dishevelled; Nemo, Nemo-like kinase; Mad, mothers against decapentaplegic homolog; Hh, hedgehog homolog; Ptc, Patched; Sufu, suppressor of fused; Disp, Dispatched; Egfr, epidermal growth factor receptor; Igfr, insulin-like growth factor receptor; Fgfr, fibroblast growth factor receptor; Epha, Eph receptor A; Ret, Ret protooncogene; Musk, skeletal muscle tyrosine kinase receptor; Ddr, epithelial discoidin domain receptor; Jak, Janus kinase; Stam, signal transducing adaptor molecule; Stat, signal transducer and activator of transcription; Pias, protein inhibitor of activated STAT; Amb, Amoebozoa; Hs, Homo sapiens; Cf, Canis familiaris; Mm, Mus musculus; Gg, Gallus gallus; Sp, Strongylocentrotus purpuratus; Dm, Drosophila melanogaster; Ce, Caenorhabditis elegans; Sp, Schizosaccharomyces pombe; Sc, Saccharomyces cerevisiae; Dd, Dictyostelium discoideum.

*Filled circles (•) indicate the presence of gene homologs, not necessarily orthologs, in select taxa. Open lozenges (◊) indicate their absence.

See the pattern? The three rightmost columns, the fungi and the slime mold, generally lack homologs to all of these genes, with a few notable exceptions. The six leftmost columns and O. carmela, all possess these genes, with a few interesting exceptions. In this property of having a particular suite of signaling genes, the metazoa cluster together very nicely, including the sponges.

Let's do it one more time, only this time looking at cell adhesion molecules rather than signaling genes.

Eumetazoan cell-adhesion machinery in the sponge O. carmela

LASP-1, LIM and SH3 domain protein 1; ADAM, a disintegrin and metalloprotease; Fat, Fat protocadherin tumor suppressor; NCAM, neural cell adhesion molecule; ECM, extracellular matrix; Cthrc, collagen triple helix repeat containing; Col11a2, procollagen, type XI, α 2; Col4, Type IV collagen; Fras1, Fraser Syndrome 1; Amb, Amoebozoa; Hs, H. sapiens; Cf, C. familiaris; Mm, M. musculus; Gg, G. gallus; Sp, S. purpuratus; Dm, D. melanogaster; Ce, C. elegans; Sp, Sc. pombe; Sc, Sa. cerevisiae; Dd, D. discoideum.

*Filled circles (•) indicate the presence of gene homologs, not necessarily orthologs, in select taxa. Open lozenges (◊) indicate their absence.

Look at that: the same pattern! Fungi and Amoebozoa lack the repertoire of sticky cell surface genes that all the metazoa, including the sponges, possess. This is not to say that single-celled creatures lack their own special adhesive proteins or signaling molecules, but merely that the ones they use are often different than the ones we use, and that you can recognize our clade by the molecules we have elevated to the canon…and that sponges definitely belong in our clade.

An important lesson here is that molecular diversity preceded morphological complexity—the lineage leading to the metazoa accumulated diverse signaling and adhesion genes because they were useful in their niche, not ours, but that those genes also were useful in achieving multicellularity. The transition was seamless and required very little in the way of novel function.

Single-celled organisms mastered all the dance steps first; what multicellularity accomplished was to add choreography, coordinating all of the players into one beautiful, coherent, and elaborate dance. Even sponges—their dance may be fairly simple and repetitive, but it still requires all the basic properties of cell:cell interaction to be carried out successfully.

Nichols SA, Dirks W, Pearse JS, King N (2006) Early evolution of animal cell signaling and adhesion genes. Proc Nat Acad Sci USA 103(33):12451-12456.